Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi.

Objectives: This study aimed to define the molecular basis of co-trimoxazole resistance in Malawian pneumococci under the dual selective pressure of widespread co-trimoxazole and sulfadoxine/pyrimethamine use.

Methods: We measured the trimethoprim and sulfamethoxazole MICs and analysed folA and folP nucleotide and translated amino acid sequences for 143 pneumococci isolated from carriage and invasive disease in Malawi (2002-08).

Results: Pneumococci were highly resistant to both trimethoprim and sulfamethoxazole (96%, 137/143).

Persistent endothelial activation and inflammation after Plasmodium falciparum Infection in Malawian children.

Endothelial dysregulation is central to the pathogenesis of acute Plasmodium falciparum infection. It has been assumed that this dysregulation resolves rapidly after treatment, but this return to normality has been neither demonstrated nor quantified. We therefore measured a panel of plasma endothelial markers acutely and in convalescence in Malawian children with uncomplicated or cerebral malaria.

Loss of endothelial protein C receptors links coagulation and inflammation to parasite sequestration in cerebral malaria in African children.

Cerebral malaria (CM) is a major cause of mortality in African children and the mechanisms underlying its development, namely how malaria-infected erythrocytes (IEs) cause disease and why the brain is preferentially affected, remain unclear. Brain microhemorrhages in CM suggest a clotting disorder, but whether this phenomenon is important in pathogenesis is debated. We hypothesized that localized cerebral microvascular thrombosis in CM is caused by a decreased expression of the anticoagulant and protective receptors thrombomodulin (TM) and endothelial protein C receptor (EPCR) and that low constitutive expression of these regulatory molecules in the brain make it particularly vulnerable.

The effect of a tuberculosis chest X-ray image reference set on non-expert reader performance.

Objectives: In low-resource settings, limitations in diagnostic accuracy of chest X-rays (CXR) for pulmonary tuberculosis (PTB) relate partly to non-expert interpretation. We piloted a TB CXR Image Reference Set (TIRS) to improve non-expert performance in an operational setting in Malawi.

Methods: Nineteen doctors and clinical officers read 60 CXR of patients with suspected PTB, at baseline and using TIRS.

Genetic characterisation of Malawian pneumococci prior to the roll-out of the PCV13 vaccine using a high-throughput whole genome sequencing approach.

Background: Malawi commenced the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant immunisation schedule in November 2011. Here we have tested the utility of high throughput whole genome sequencing to provide a high-resolution view of pre-vaccine pneumococcal epidemiology and population evolutionary trends to predict potential future change in population structure post introduction.

Methods: One hundred and twenty seven (127) archived pneumococcal isolates from randomly selected adults and children presenting to the Queen Elizabeth Central Hospital, Blantyre, Malawi underwent whole genome sequencing.

Streptococcus pneumoniae: the evolution of antimicrobial resistance to beta-lactams, fluoroquinolones and macrolides.

Multi drug resistant Streptococcus pneumoniae constitute a major public health concern worldwide. In this review we discuss how the transformable nature of the pneumococcus, in parallel with antimicrobial induced stress, contributes to the evolution of antimicrobial resistance; and how the introduction of the pneumococcal conjugate vaccine has affected the situation.

Early deaths during tuberculosis treatment are associated with depressed innate responses, bacterial infection, and tuberculosis progression.

Up to 14% of Malawian adults die during the intensive phase of tuberculosis treatment. In a prospective cohort of 199 Malawian adults with microbiologically confirmed pulmonary tuberculosis, clinical and laboratory parameters were compared between those who died or deteriorated with those who had an uneventful recovery. Baseline tumor necrosis factor alpha responses to stimulation with heat-killed Mycobacterium tuberculosis and lipopolysaccharide were reduced among the 22 patients with poor outcome (P = .

A systematic review of risk factors for death in adults during and after tuberculosis treatment.

Background: Despite effective anti-tuberculosis chemotherapy, case-fatality rates of up to 25% are described in both industrialised and resource-poor settings. An understanding of the factors predisposing to poor outcome may allow the development of adjunctive treatment strategies or closer clinical monitoring in high-risk individuals.

Objectives: To describe the definitions and timing of deaths due to tuberculosis (TB), and the reported range of risk factors for death.

Hidden risks for pneumonia in Malawi.

Domestic smoke exposure and early HIV infection are critical but unseen risk factors for pneumonia. This paper reviews how recent research in Malawi and elsewhere contributes to an understanding of the possible immunological mechanisms underlying these risks.